a concise yet very informative presentation, on drug approval process and clinical trial regulations in India, prepared for clinical research students Please refer notes for abbreviations and additional information

1. INDA SUBMISSION IN
INDIAN REGULATION
Dr Anupama Soman

2. INDIAN REGULATORY AUTHORITY
 CDSCO(Central Drugs Standard Control organization)-- DCGI
INDIAN REGULATIONS
 Drugs and cosmetics act 1940
 Drugs and cosmetics rules 1945
 Schedule Y( Revised in 2005)
GUIDELINES
 Indian GCP
 ICMR Ethical guidelines

3.  Legal system – comprised of laws
 Law(legislation) – different sections ( eg : laws of administration, law of health etc
)
 Laws – comprised of acts, regulations, amendments, notifications, bills etc
 Act- also a law or a part of law(D&C act, mental health act, Indian patent act )
 Rules – simple guidelines for the successful implementation of an act
 schedules – sections of appendices to rules (explanations for some sections in
rules )
 D&C ACT 1940 – 6 SIX CHAPTERS
 D&C RULES 1945 – 19 PARTS(RULES ) AND SCHEDULES A-Y(GUIDELINES
ENFORCED BY LAW)
LEGAL SYSTEM IN INDIA

4. Hierarchy of legal system
ACT
• Drugs and cosmetics act 1940
(statement of law)
RULE
• Drugs and cosmetics rules 1945 (guidelines
for implementation of D&C act)
SCHEDULE
• Schedules A-Y(appendices- detailed explanations for
reference)

5. Rules
 122DA - PERMISSION TO CONDUCT CLINICAL TRIAL
 122-E - DEFINITION OF IND& ND
Latest Amendments 2013
 122 DAA - DEFINITION OF CLINICAL TRIAL
 122 DAB - COMPENSATION IN CASE OF TRIAL RELATED INJURY
 122DAC - CONDITIONS OF CLINICAL TRIAL PERMISSION
&INSPECTION
 122DD - REGISTRATION OF ETHICS COMMITTEE

6. INVESTIGATIONAL NEW DRUG
 IND has been defined under Rule 122-DA (3) of Drugs
and Cosmetics Rules 1945 as a new chemical entity or
a product having therapeutic indication but which have
never been earlier tested on humans.

7. IND - TYPES
IND
DISCOVERED IN
INDIA
IND
DISCOVERED
OUTSIDE
INDIA

8. IND
IND DISCOVERED IN INDIA
 PHASE I – PHASE III IS MUST
 PHASE III MIN 500 SUBJECTS (IN10
-15 CENTRES ) IS MANDATORY
IND DISCOVERED IN OTHER
COUNTRIES
 CT ALLOWED ONLY IF PHASE 1
DATA IS AVAILABLE
 REPEAT PHASE I / START FROM
PHASE II
 PHASE III MIN 100 SUBJECTS IN 3-
4 CENTRES IS MANDATORY

9. IND & ND
IND
 A NCE or product having
therapeutic indication
 Which has never been tested
earlier on human beings
ND
 A new substance of chemical ,
biological or BT origin
 Which has not been used to
any significant extent in the
country except during CT
 Modified or new
indication,dosage form,RA
 FDC
 All new vaccines
A new drug continues to be considered as new drug for a period of 4 years
from its approval or its inclusion in Indian Pharmacopoeia.

10. INDA PROCESS IN INDIA
 No clinical trial for a new drug/IND for any purpose be
conducted without permission , in writing, of the Licensing
Authority (DCGI).
 Application for conducting clinical trials in India require
submission by the sponsor on Form 44 along with requisite fee
(Rs 50k) and documents as provided under Schedule Y to
Drugs and Cosmetics Rules 1945.

11. DRUG APPROVAL PROCESS IN INDIA

12. RULE 122 E –Definition of Drugs
New substances having therapeutic indication,
Modified or New claim,
New RA for already approved drug,
FDC
Detailed review by IND committee
IND Applicant CDSCO HQ
Refer to IND committee
Technical committee
Apex committee
Recommendation to DCGI
Approval

13. CDSCO - A new face
 IN COMPLIANCE TO HONBLE SUPREME COURTS ORDER
DATED ON 3/1/2013
A SUPERVISION OVER CDSCOS ACTION BY
 TECHNICAL COMMITTEE - Under health secretory
 APEX COMMITTEE – under DGHS
WITHIN CDSCO
 IND COMMITTEE
Evaluation of IND( discovered in India)
chaired by – DG (ICMR), Secretary (DHR)
 12 NEW DRUG ADVISORY COMMITTEES
Evaluation of all applications of CT and new drug approvals
except IND & subsequent approval of already approved drug
& BE studies

14. After receiving the application,
the CDSCO Headquarters in
New Delhi refer it to
IND committee/New Drug
Advisory committee, who
reviews and submits its report
to DCGI-Who Approves/
Declines/Comments
Approvals granted by DCGI are
reviewed by tech. committee and
recommendations are sent to
Apex committee, who
approves/recommends

15. INITIATION
 APPLICATION IN FORM 12
 TEST LICENCE IN FORM 11
NOTE: Once DCGI approves INDA NOC FOR CT +TEST LICENCE in FORM
11 is issued together
 APPLICATION IN FORM 30 + TEST LICENCE OR NOC ( FOR INDIAN IND
)
 MANUFACTURING LICENSE IN FORM 29
TEST LICENCE (TO IMPORT /MANUFACTURE FOR TEST
PURPOSE)
MANUFACTURING LICENSE FROM STATE DRUG RA

16. FORM 44
 Application for the grant of permission to import or
manufacture a New drug or to under take clinical trial
A. Permission to conduct a clinical trial (INDA)
B. Permission to market a new drug (NDA)
C. Subsequent approval/permission for manufacture of
already approved new drug
D. Approval/permission for fixed dose combination
E. Subsequent approval/approval for new indication

17. FORM 44 PROCESS
APPLICATION FORM 44
1. import of FF
2. Import of RM
3. Mfg of FF
4. Mfg of RM
5. CT
1.APPROVAL FORM 45 (IMP FF)
2.APPROVAL FORM 45A (IMP
RM)
3.APPROVAL FORM 46 (MFG
FF)
4.APPROVAL FORM 46A (MFG
FF)
5.NOC FOR CT + TEST
LICENCE IN FORM 11)

18. INDA (Data to be submitted) –sch Y
 Data to be submitted along with the application on Form44 to
conduct clinical trials (2 hard copies and 2 soft copies i.e.,
CDs in PDF format)
1. Application on Form 44
2. Introduction of the drug
3. Fee Rs 50K through challan form
4. Chemical and Pharmaceutical information as per Appendix I of Schedule Y
5. Animal Pharmacology as per Appendix IV
6. Animal Toxicology as per Appendix III
7. Human/Clinical Pharmacology data as per Appendix I ( For foreign trials)
8. Regulatory status in other countries as per Appendix I.

19. DOCUMENTS – sch Y & Indian GCP
 Proposed protocol (appendix X)
 Investigators brochure
 Informed consent document
 Investigator’s undertaking
 Case report forms
 Ethics committee clearance if available
NOTE : application for test licence in form 12 may b submitted along with
CT application or separately

20. Inda review
CHECKLIST FOR REVIEW -CDSCO
INDAChecklist of New Drugs.pdf

21. REVIEW TIME OF INDA- From 2006
CT which has got
approval by RA of
9 regions of world
Mainly global trials
2-4 weeks
Practically 6-8
weeks
CATEGORY
A
All other trials
Mainly domestic
8-12 weeks
Practically 5-6
months
CATEGORY
B

22. • It takes 4-6 months for the approval but it is not documented.
• The Ethical Committee also requires 1-3 months time.
• Thus, it almost takes 7-9 months for approval of INDA from
DCGI.
• For international applicants, import license to import IP
samples and permission from Director General Foreign Trade
to export blood samples is also needed.
IND SUBMISSION…

23. NEW DRUG APPLICATION (NDA)
 The New Drug Application is the vehicle through which
the drug sponsors formally propose DCGI to approve
a new drug for sale and marketing after Phase IIIA
trials.

24. NEW DRUG:
Import FF/Mfg FF Rs. 50,000/-
Import RM + Mfg FF Rs. 50,000/-
APPROVED DRUG:
Application by the same
applicant after 1 year
of approval Rs.15,000/-
Import/Mfg of FDC Rs.15,000/-
CONDUCT OF CLINICAL TRIAL(with ND/IND) :
Phase I Rs.50,000/-
Phase II Rs.25,000/-
Phase III Rs.25,000/-
NO SEPARATE FEES TO BE PAID ALONG WITH APPLICATION FOR
IMPORT/MFG AFTER THE SUCCESSFUL COMPLETION OF CLINICAL TRIAL
APPLICATION FEES

25. REFERENCES
1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612334/
2. http://www.mondaq.com/india/x/244304/Healthcare/Latest+Amendments+In+2013+To
+The+Drugs+And+Cosmetics+Rule+1945
3. https://www.amarexcro.com/articles/docs/RAPS_Focus_Practical_Feb2009.pdf
4. https://www.scribd.com/doc/7275483/Latest-Amendment-in-Schedule-Y#scribd
5. http://cdsco.nic.in/writereaddata/Guidance_for_New_Drug_Approval-23.07.2011.pdf
6. http://www.cdsco.nic.in/writereaddata/CDSCO-GuidanceForIndustry.pdf
7. https://www.pharmamedtechbi.com/~/media/Supporting%20Documents/Pharmasia%2
0News/2012/May/DCGI%20report.pdf
8. http://www.isporindia.com/wp-content/uploads/2013/04/Dr.Surinder-Singh.pdf
9. http://www.cdsco.nic.in/writereaddata/GUIDANCE%20DOC.pdf
10. Indian GCP and schedule y

26. THANK YOU 